rs285875

Variant names:

• chr8-105043358-T-C
• rs285875
• ENST00000518180.1:n.242+51689T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000518180.1(ZFPM2):​n.242+51689T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 152,204 control chromosomes in the GnomAD database, including 62,728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (62728 hom., cov: 32)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 0 publications found

Genes affected

ZFPM2 (HGNC:16700): (zinc finger protein, FOG family member 2) The zinc finger protein encoded by this gene is a widely expressed member of the FOG family of transcription factors. The family members modulate the activity of GATA family proteins, which are important regulators of hematopoiesis and cardiogenesis in mammals. It has been demonstrated that the protein can both activate and down-regulate expression of GATA-target genes, suggesting different modulation in different promoter contexts. A related mRNA suggests an alternatively spliced product but this information is not yet fully supported by the sequence. [provided by RefSeq, Jul 2008]

ZFPM2 Gene-Disease associations (from GenCC):

• 46,XY sex reversal 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• diaphragmatic hernia 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• tetralogy of fallot

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000518180.1	n.242+51689T>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137933 AN: 152086 Hom.: 62689 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.901

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.907 AC: 138026 AN: 152204 Hom.: 62728 Cov.: 32 AF XY: 0.911 AC XY: 67789 AN XY: 74420

African (AFR) AF: 0.936 AC: 38908 AN: 41556

American (AMR) AF: 0.910 AC: 13886 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3141 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5172 AN: 5178

South Asian (SAS) AF: 0.928 AC: 4478 AN: 4824

European-Finnish (FIN) AF: 0.950 AC: 10067 AN: 10602

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59335 AN: 67990

Other (OTH) AF: 0.902 AC: 1905 AN: 2112

Alfa AF: 0.897 Hom.: 7902

Bravo AF: 0.906

Asia WGS AF: 0.952 AC: 3306 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.55
PhyloP100		-2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs285875; hg19: chr8-106055586;